title: Beyond C4d: the ultrastructural appearances of endothelium in ABO-incompatible renal allografts.
abstract: BACKGROUND
  ABO incompatibility is no longer a barrier in kidney transplantation. C4d is frequently positive in ABO-incompatible (iABO) biopsies without further signs of microcirculation injury. This phenomenon is assumed to represent graft accommodation. However, ultrastructural examination of glomerular and peritubular capillary endothelium might reveal subtle endothelial damage.
  
  
  METHODS
  We studied the ultrastructural appearance of the endothelium in 67 biopsies from 21 patients with iABO allografts and compared it with 20 patients (29 biopsies) with ABO-compatible (cABO) grafts with C4d positivity and 25 ABO-compatible control patients (25 biopsies) without serological or histological evidence of humoral rejection (C4d negative). Ten ultrastructural parameters indicative of chronic and acute glomerular and peritubular capillary damage in transmission electron microscopy (TEM) were semi-quantitatively graded and expressed in a sum score. Clinico-pathological data were compared as well as graft function at the time of biopsy and follow-up.
  
  
  RESULTS
  Ultrastructural parameters did not significantly differ between iABO and controls. In contrast, C4d-positive cABO had the highest TEM sum score (P = 0.001 versus iABO, P = 0.002 versus controls). The sum score did not differ between C4d-positive and C4d-negative iABO but did differ between patients with and without anti-HLA donor-specific antibodies (DSA). Graft function in iABO at the time of biopsy and at follow-up was similar to controls.
  
  
  CONCLUSIONS
  Our ultrastructural observations support the concept of endothelial accommodation in iABO renal transplants. C4d positivity in the ABO-incompatible situation does not indicate injurious activation of the complement cascade and does not seem to impact on the graft function, in contrast to C4d deposition in cABO with antibody-mediated rejection.
authors.affiliation: Institute for Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Bröcker
authors.forename: Annika
authors.initials: A
authors.lastname: Pfaffenbach
authors.forename: Antje
authors.initials: A
authors.lastname: Habicht
authors.forename: Christos
authors.initials: C
authors.lastname: Chatzikyrkou
authors.forename: Hans H
authors.initials: HH
authors.lastname: Kreipe
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Irina
authors.initials: I
authors.lastname: Scheffner
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
authors.forename: Eva
authors.initials: E
authors.lastname: Zilian
authors.forename: Stephan
authors.initials: S
authors.lastname: Immenschuh
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Peter A
authors.initials: PA
authors.lastname: Horn
authors.forename: Falko M
authors.initials: FM
authors.lastname: Heinemann
authors.forename: Jan U
authors.initials: JU
authors.lastname: Becker
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000368:Aged; D064591:Allografts; D001787:Blood Group Incompatibility / Q000276:immunology; D016022:Case-Control Studies; D003167:Complement Activation; D015935:Complement C4b / Q000276:immunology*; D004727:Endothelium / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology* / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000017:ABO Blood-Group System; D006680:HLA Antigens; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d
keywords: ABO incompatible; C4d; accommodation; acute antibody mediated rejection; electron microscopy; kidney transplantation